TEMPLATE CLINICAL TRIAL AGREEMENT 2015 – THE NETHERLANDS
CLINICAL TRIAL AGREEMENT
(Template agreement for industry initiated and sponsored Clinical Trials, with human
subjects, conducted by non-academic (STZ) hospitals and NKI/AvL in The Netherlands)
Clinical Trial: [insert title]
Protocol: [insert EUDRACT number or Dutch Registration NL-number and date]
Institution: [insert site name and number or location]
Study Drug: [insert name]
Effective date of agreement: __/__/____ (dd-mm-yyyy)
Scope of use:
This template clinical trial agreement is created in joint cooperation between the
vereniging Samenwerkende Topklinische opleidingsZiekenhuizen (STZ), Nefarma,
Stichting Het Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis
(NKI/AvL) and ACRON, to facilitate conducting clinical trials in The Netherlands.
The clauses on termination and publication meet the Directive on the Assessment of
the Clinical Trial Agreement of the CCMO.
In case a Clinical Trial Organisation (CRO) is signing this agreement on behalf of
the Sponsor or in its own name, please note that depending on the Power of Attorney
/ Delegation of Authority given by sponsor to the CRO, a separate indemnity letter
signed by Sponsor may be needed.
If no CRO is involved, “Sponsor and/or CRO” must be read as solely “Sponsor”
throughout the Agreement.
Template Clinical Trial Agreement version July 2015
Page 1
The undersigned,
A. [insert name of the sponsor], whose registered office is at [insert address], lawfully
represented by [insert name(s) and function(s)]
(hereinafter referred to as “Sponsor”) OR CRO[insert name of CRO] acting in its own
name and for and on behalf of [insert name of Sponsor], whose registered office is at
[insert address of CRO] (hereinafter referred to as “CRO”)
and
B. [insert name of institution], whose address is at [insert address], lawfully represented
by [insert name(s) and function(s)]
(hereinafter referred to as “Institution”)
[In case the Principal Investigator is not an employee of Institution and acts as a party:]
and
C. [INVESTIGATOR], [insert: name of physician …», …[function], [tax/office address
and chamber of commerce registration number, if applicable]
(hereinafter referred to as “Principal Investigator”) ]
[ OR in case the Principal Investigator is an employee of the Institution: ]
in the presence of
[INVESTIGATOR] [insert investigator’s title, name and department of Institution where the
investigator is employed], the supervisor under whose responsibility the conduct of the
clinical trial will be carried out (hereinafter referred to as “the Principal Investigator”)
WHEREAS, the Sponsor is a pharmaceutical company involved in research, development,
registration, manufacture and/or sale of medicines for use in humans;
WHEREAS, the Sponsor has designed the clinical trial identified hereof, to evaluate
Sponsor’s drug ____________________ (“Study Drug”) in accordance with the protocol
defined below; and
WHEREAS, the Sponsor contracted the CRO to perform one or more of a Sponsor's clinical
trial-related duties and functions as summarized in the Power of Attorney / Delegation of
Authority attached herein as Annex 8;
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WHEREAS, the Principal Investigator and Institution are concerned with the diagnosis,
treatment and prevention of disease and/or clinical research for the improvement of
healthcare;
WHEREAS, the Institution has facilities and personnel with the requisite skills, experience,
and knowledge required to support the performance of the clinical trial by the Principal
Investigator; and
WHEREAS, Principal Investigator, having reviewed the Protocol for the Clinical Trial, the
investigator brochure and sufficient information regarding the Investigational Product in
order to evaluate and determine its interest in participating in the Clinical Trial, wishes to
participate in the Clinical Trial and the Principal Investigator assures that he/she has sufficient
authority, competence and experience in conducting clinical trials.
In consideration of the undertakings and commitments set forth herein, the Parties agree to
enter into this Clinical Trial Agreement.
This Agreement, when signed by all Parties, is effective as of (insert date)
1. DEFINITIONS
The following words and phrases have the following meanings:
a. “Affiliate” means any business entity which controls, is controlled by, or is under the
common control with Sponsor and/or, for the purpose of this Agreement, the
representative of Sponsor, the CRO, including their subsidiaries. For the purposes of
this definition, a business entity shall be deemed to control another business entity if it
owns, directly or indirectly, in excess of 50% of the voting interest in such business
entity or the power to direct the management of such business entity or to elect or
appoint 50% or more of the members of the management of such business entity;
b. “Agent” shall include, but shall not be limited to, any person providing services to a
Party under a contract for services or otherwise, to include without limitation any
pharmacist, clinical chemist, nurse or other health professional.
c. “Agreement” means this agreement comprising its clauses, schedules and any
appendices attached to it, including the Protocol and including any amendments to the
Agreement agreed between the Parties;
d. “Auditor” means a person who is authorised to carry out a systematic review and
independent examination of clinical trial related activities and documents to determine
whether the evaluated clinical trial related activities were conducted, and the data
were recorded, analysed and accurately reported according to the Protocol, the
Standard Operating Procedures of Sponsor and/or CRO, ICH GCP and the applicable
regulatory requirements;
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e.
f.
g.
h.
i.
j.
k.
“Clinical Data” means personal data as defined in Directive 95/46/EC and in the
Dutch privacy Law, i.e. any information relating to an identified or identifiable
Clinical Trial Subject.
“Clinical Trial” means the investigation to be conducted at the Trial Site in
accordance with the Protocol as defined below;
“Clinical Trial Authorisation” means a Clinical Trial authorised in accordance with
the article 2 and 13i of the Dutch Medical Research Involving Human Subjects Act;
“Clinical Trial Subject” means a person enrolled to participate in the Clinical Trial;
“Competent Authority” means the authority appointed to evaluate the Clinical Trial
in accordance with 13i of the Dutch Medical Research Involving Humans Subjects
Act, based on article 9 of the European Clinical Trial Directive 2001/20/EC;
“Confidential Information” means information provided by a Party (the Disclosing
Party) to the other Party (the Receiving Party) or to any other of such Receiving
Party’s employees or agents, and means all information (including, without limitation,
study protocols, case report forms, clinical data, other data, reports, specifications,
computer programs or models and related documentation, know-how, trade secrets, or
business or research plans) of the Disclosing Party or the Disclosing Party’s Affiliates
that are provided in connection with this Agreement or the Clinical Trial. Sponsor’s
Confidential Information shall include Clinical Trial data, results, or reports created
by Institution, Principal Investigator, or Research Staff in connection with the Clinical
Trial (except for a Clinical Trial Subject’s medical records); and cumulative Clinical
Trial data, results, and reports from all sites conducting the Clinical Trial;
“CRF” means the case report form in a format prepared by Sponsor and documenting
the administration of the Investigational Product to Clinical Trial Subjects as well as
all tests and observations related to the Clinical Trial;
“eCRF” means a CRF in electronic form;
l.
m. “CRO” means Contract Research Organization which is the scientific organization
(commercial, academic or other) to which a sponsor may transfer some of its tasks and
obligations. Any such transfer should be defined in writing. (And according to 21CFR312.52:
Transfer of Obligations to a CRO: CRO shall comply with the same regulations/ CRO is
subject to the same regulatory actions)
n. “Independent Committee” means a committee such as a Data and Safety Monitoring
Board (DSMB), which is a group of individuals with pertinent expertise that have
oversight of and reviews on a regular basis accumulating data from one or more
ongoing clinical trials and that advise the Sponsor regarding the continuing safety of
Clinical Trial Subjects and those to be recruited to the Clinical Trial, as well as the
continuing validity and scientific merit of the Clinical Trial.
o. “Effective Date” the date this Agreement comes into effect, being the date mentioned
in the recitals above;
p. “Ethics Committee” means the accredited medical research ethics committee
competent to review the Clinical Trial in accordance with applicable Law, and to
which the Protocol has been submitted for approval;
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q. “ICF” means the Informed Consent Form as approved by the Ethics Committee, in
which the Clinical Trial Subject consents to his participation in the Clinical Trial;
r. “Intellectual Property Rights” means patents, trade marks, trade names, service
marks, domain names, copyrights, rights in and to databases (including rights to
prevent the extraction or reutilisation of information from a database), design rights,
topography rights and all rights or forms of protection of a similar nature or having
equivalent or the similar effect to any of them which may subsist anywhere in the
world, whether or not any of them are registered and including applications for
registration of any of them;
s. “Investigational Product” means the Study Drug identified above and the control
material, as further detailed in the Protocol;
t. “Know How” means all technical and other information which is not in the public
domain (other than as a result of a breach of confidence), including but not limited to
information comprising or relating to concepts, discoveries, data, designs, formulae,
ideas, inventions, methods, models, procedures, designs for experiments and tests and
results of experimentation and testing, processes, specifications and techniques,
laboratory records, manufacturing data and information contained in submissions to
regulatory authorities, whether or not protected by Intellectual Property Rights or any
applications for such rights;
u. “Law” means any International, European Union and Dutch law and regulations, as
well as generally accepted international conventions applicable to the performance of
the Clinical Trial. Such Law including:
 Directives 2001/20/EC and 2005/28/EC of the European Parliament and the
Council relating to medicinal products for human use and in guidance published
by the European Commission pursuant to such Directives and any
implementation in Institution’s national Law,
 The Council Directive 95/46/EC of the European Parliament and of the Council
of 24 October 1995 on the protection of individuals with regard to the
processing of personal data and on the free movement of such data and any
implementation in Institution’s national Law,
 the Dutch Medical Research Involving Human Subjects Act (Wet Medischwetenschappelijk Onderzoek met Mensen or WMO),
 the Dutch Personal Data protection Act (Wet Bescherming Persoonsgegevens)
 the Dutch Medical Treatment Agreements Act (Wet op de geneeskundige
behandelingsovereenkomst or Wgbo)
 ICH Harmonised Tripartite Guideline for Good Clinical Practice
(CPMP/ICH/135/95),
 the Directives on “Review of Clinical Trial Agreements” and on “External
Review” issued by the Dutch Central Committee on Research involving Human
Subjects (Centrale Commissie Mensgebonden Onderzoek or CCMO),
 the principles of the Dutch Code of Conduct regarding the adequate
procurement, management and use of bodily human tissue published by the
Federation of Dutch Medical Scientific Societies,
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 the Dutch Code for Pharmaceutical Advertising (Code Geneesmiddelenreclame)
(CGR), applicable for the Sponsor, and
 The Declaration of Helsinki, the most recent version;
References to EU Council Directives and Dutch Law include any amendments or
replacements of such Law.
v. “Party” means the Sponsor and/or CRO, the Institution or, only if the Principal
Investigator is a separate party to this Agreement, the Principal Investigator, and
“Parties” shall mean two or all of them jointly;
w. “Principal Investigator” means the person who will take primary responsibility for
the conduct of the Clinical Trial at the Trial Site or any other person as may be agreed
between the Parties as a replacement;
x. “Protocol” means the document signed by the Principal Investigator, entitled “[insert
protocol name]” with registration [insert EUDRACT number or Dutch Registration
NL-number and date] detailing all aspects of the Clinical Trial, a copy of which is at
Annex 1 to this Agreement. The Protocol includes all amendments thereto for which
Clinical Trial Authorisation has been obtained;
y. “Research Staff” means the persons who will undertake the conduct of the Clinical
Trial at the Trial Site on behalf of the Principal Investigator and under the supervision
of the Principal Investigator;
z. “Samples” means any human biological materials, including but not limited to blood,
body tissue, plasma and any other material containing human cells;
aa. “Site Parties” shall refer to the Principal Investigator and the Institution jointly;
bb. “Target” means the estimated number of Clinical Trial Subjects to be included in the
Clinical Trial as referred to in clause 5.2;
cc. “Timelines” means the dates set out in Annex 2 hereto as may be amended by
agreement between the Sponsor and the Principal Investigator and “Timeline” shall
mean any one of such dates;
dd. “Trial Monitor” means one or more persons appointed by the Sponsor and/or CRO to
monitor compliance of the Clinical Trial with GCP and the Protocol and to conduct
source data verification;
ee. “Trial Site(s)” means the premises at the Institution where the Clinical Trial will be
conducted;
2. OBLIGATIONS
2.1.
The Sponsor and the Principal Investigator agree to perform the Clinical Trial in
accordance with the terms and conditions of this Agreement.
2.2.
The Parties represent and warrant that they each have the authority to enter into
this Agreement. The Institution and/or Principal Investigator will ensure the
availability of and/or access to any resources necessary to perform the Clinical
Trial at the Trial Site, including departments, facilities and Research Staff and
support personnel, and the Principal Investigator represents that he/she holds the
necessary registration and has the necessary qualifications, expertise and time to
perform the Clinical Trial.
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2.3.
2.4.
2.5.
2.6.
2.7.
2.8.
3.
The Institution and/or the Principal Investigator shall notify the Sponsor and/or
CRO if the Principal Investigator ceases to be associated with the Institution
where the Clinical Trial will be conducted or if he/she is otherwise unavailable to
continue as Principal Investigator, and Institution and/or Principal Investigator
shall use all reasonable endeavours to find a qualified successor acceptable to the
Sponsor and/or CRO, subject to the Principal Investigator’s overriding
obligations in relation to Clinical Trial Subjects and individual patient care. In
the event Principal Investigator is for whatever reason unable or unwilling to
appoint a successor personally, the Institution will have the right to recommend a
suitable successor.
The Site Parties shall procure the performance of the obligations of the Research
Staff as set out in this Agreement.
Institution, and if the Principal Investigator is a party, the Principal Investigator,
will guarantee the availability of sufficient and adequately trained and
experienced Research Staff. This will include the participation of the Principal
Investigator and Research Staff in any training provided by Sponsor reasonably
required for the sound conduct of the Clinical Trial.
Subject to the Principal Investigator’s overriding obligations in relation to
Clinical Trial Subjects and individual patient care, the Principal Investigator shall
not, and the Principal Investigator shall ensure that the Research Staff shall not,
during the term of this Agreement conduct any other trial which might jeopardize
the Principal Investigator’s ability to recruit, enrol and study the required cohort
of Clinical Trial Subjects.
Terms and conditions on any equipment provided by Sponsor, shall be described
in Annex 5.
The Site Parties acknowledge that Sponsor and/or CRO and its Affiliates need to
adhere to the provisions of (i) the Bribery Act 2010 of the United Kingdom
(Bribery Act); (ii) the Foreign Corrupt Practices Act 1977 of the United States of
America (FCPA) and (iii) any other applicable anti-corruption legislation
(together the Applicable Anti-Corruption Legislation). A summary of the key
principles underlying the Bribery Act and the FCPA is set out in Annex 6. The
Institution and the Principal Investigator shall not and shall not permit or induce
employees, agents, consultants or other representatives, whether directly or
indirectly, to engage in any activity that is prohibited by the Applicable AntiCorruption Legislation including bribery, kickbacks, payoffs or other corrupt
business practices, as outlined in the summary in Annex 6. Sponsor shall be
responsible for keeping the summary up to date in case of any changes to the
Bribery Act and the FCPA.
CLINICAL TRIAL GOVERNANCE AND COMPLIANCE
3.1.
The Sponsor shall be responsible for obtaining and maintaining Clinical Trial
Authorisation for the Clinical Trial and substantial amendments to the Protocol.
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3.2.
3.3.
3.4.
3.5.
3.6.
3.7.
The Sponsor may require the Principal Investigator to apply for the Clinical Trial
Authorisation for Sponsor, in which case the Principal Investigator shall keep the
Sponsor fully apprised of the progress of Ethics Committee submissions and
shall upon request provide the Sponsor with all correspondence relating to such
submissions.
The Principal Investigator shall not consent to any change in the Protocol
requested by the Ethics Committee or Competent Authority without the prior
written consent of the Sponsor.
In the event of any substantial amendments being made to the Protocol, the
amendments shall be signed by the Principal Investigator and shall be
implemented by the Research Staff as required by the Sponsor or CRO after
approval of the amendments by the Competent Authority and a favourable
opinion of the Ethics Committee.
The Clinical Trial shall be performed at the Trial Site. The Principal Investigator
shall be responsible for obtaining authorization from the representatives of the
Trial Site to perform the Clinical Trial at the Trial Site, which shall include but
not be limited to the engagement of sub-investigators, to the extent applicable the
pharmacist of the Institution (unless a separate Pharmacy Agreement is made as
set out in article 7.1 below), clinical chemists, and the Research Staff required to
perform the Clinical Trial as set out in this Agreement.
The Sponsor shall submit the Clinical Trial for listing on a free, publicly
accessible clinical trial registry like www.clinicaltrials.gov or on websites
managed
by
a
registry
conforming
to
WHO
standards
(http://www.who.int/ictrp/network/criteria_summary/en/index.html)
after
Clinical Trial Authorization. Upon request of the Institution or the Principal
Investigator the Sponsor will disclose the registry and the date of submission.
The Parties shall conduct the Clinical Trial in accordance with:
a.
the Agreement;
b.
the Protocol;
c.
the terms and conditions of the Clinical Trial Authorisation granted by
the Competent Authority and the opinion of the Ethics Committee; and
d.
the applicable Law.
The Site Parties shall make and retain records regarding the Clinical Trial as
required by the Protocol, applicable Law, and in accordance with the Institution’s
standard archiving procedures. Institution will retain such records for a minimum
of fifteen (15) years from the date of database closure. At least ninety (90) days
prior to the expiry of such retention period, Sponsor will contact Institution. If
requested by Sponsor, Institution shall retain the records for a longer period of
time at Sponsor’s expense.
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4. LIABILITIES, INDEMNIFICATION AND INSURANCE
4.1.
4.2.
4.3.
4.4.
4.5.
Subject to the limitations set out hereinafter, Sponsor shall indemnify and hold
harmless Institution, its employees, Agents, the Principal Investigator and the
Research Staff (the “Indemnitees”) against all claims, demands, actions or
proceedings (to include any settlements or ex gratia payments made with the
consent of the Parties hereto and reasonable legal and expert costs and expenses)
made or brought (whether successfully or otherwise): (i) by or on behalf of any
Clinical Trial Subject in connection with personal injury or death arising out of the
administration or use of the Investigational Product during or as a result of the
Clinical Trial, or of any clinical intervention or procedure provided for or required
by the Protocol, to which the Clinical Trial Subject would not have been exposed
but for its participation in the Clinical Trial; (ii) by Institution, the Principal
Investigator or by or on behalf of a Clinical Trial Subject for compensation of
reasonable and necessary medical costs and expenses incurred by the Clinical
Trial Subject who has suffered personal injury as described in 4.1.(i) above.
Sponsor’s indemnification and defence of the Indemnities shall not apply to any
claim or proceeding pursuant to clause 4.1, and Sponsor shall not be liable
(a)
to the extent that said personal injury (including death) is caused by
any of the Indemnitees’ failure to comply with this Agreement; or
(b)
to the extent that said personal injury (including death) is caused by
(medical or other) professional malpractice, negligence, recklessness or
willful conduct or misconduct (in Dutch: beroepsfout, nalatigheid,
roekeloosheid of opzettelijk handelen of nalaten) of any of the
Indemnitees;
(c)
if any of the Indemnities shall have made any admission in respect of
such claim or proceeding or taken any action relating to such claim or
proceeding prejudicial to the defence of it, without the written consent
of Sponsor, provided that this condition shall not be treated as breached
by any statement properly made by any of the Indemnities in
connection with the operation of Institution’s internal complaint
procedures, accident reporting procedures or disciplinary procedures or
where such a statement is required by law.
Sponsor shall keep Site Parties reasonably informed of the progress of any such
claim or proceeding.
The Parties will each use their reasonable endeavours to inform each other
promptly of any circumstances reasonably thought likely to give rise to any claim
or proceeding resulting from the Clinical Trial of which it is directly aware.
Parties shall keep each other reasonably informed of developments in relation to
any such claim or proceeding. The Parties will use reasonable efforts to consult
with each other on the nature of any defence to be advanced.
Institution, Principal Investigator and Sponsor will each give to the other such help
as may reasonably be required for the efficient conduct and prompt handling of
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any claim or proceeding made or brought by or on behalf of Clinical Trial
Subjects (or their dependants).
4.6. Nothing in this clause 4 shall operate so as to restrict or exclude the liability of any
Party vis-à-vis the Clinical Trial Subjects in relation to their death or personal
injury caused by the negligence of that Party or its servants or employees or to
restrict or exclude any other liability of a Party which cannot be so restricted or
excluded in law.
4.7. In no circumstances shall any Party be liable to the other in contract or otherwise
howsoever arising or whatever the cause thereof, for any indirect or consequential
damages of any nature, such as but not limited to any loss of profit, business,
goodwill, reputation, contracts, revenues or anticipated savings which arise
directly or indirectly from any default on the part of Sponsor, Institution or the
Principal Investigator, except and to the extent such damages
(a)
shall be covered under and paid out of any insurance policy of the liable
party, or
(b)
are caused by gross negligence, recklessness or willful conduct or
misconduct (in Dutch: bewuste roekeloosheid of opzettelijk handelen of
nalaten) of any of the Indemnitees and cannot be so restricted or
excluded by law.
4.8. The liability of the Site Parties for a claim or proceeding of Sponsor under this
Agreement shall be limited to an amount of three (3) times the total contract sum
or the amount covered and paid out under the insurance policy taken out in
accordance with clause 4.10 below, whichever is the highest; except and to the
extent such claim or proceeding is made for damages caused by gross negligence,
recklessness or willful conduct or misconduct (in Dutch: bewuste roekeloosheid of
opzettelijk handelen of nalaten) of any of the Site Parties and cannot be so
restricted or excluded by law.
4.9. Sponsor will take out or maintain
(a)
insurance cover in respect of its potential liability for damages to
Clinical Trial Subjects resulting from the Clinical Trial in accordance
with the requirements set out in the (Dutch) Medical Research
Involving Human Subjects Act and the Decree on Obligatory Insurance
for Medical Studies involving Human Subjects unless this requirement
has been waived by the Ethics Committee, and
(b)
further appropriate insurance cover in respect of its other potential
liability under this Agreement. Sponsor shall produce to Institution, on
request, copies of such insurance certificates. Except for the limitations
stated in clause 4.7 above, the terms of any insurance or the amount of
cover shall not relieve Sponsor of any liabilities under this Agreement.
4.10. Institution will take out or maintain an insurance cover in respect of the potential
liability of Institution, the Research Staff, the Principal Investigator and any other
employees and Agents involved with the conduct of the Clinical Trial pursuant to
this Agreement. Institution shall produce to Sponsor, on request, copies of
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insurance certificates, together with evidence that the policies to which they refer
remain in full force and effect during the term of this Agreement and any period
thereafter as may be required by mandatory law. Except for the limitations stated
in clause 4.7 and 4.8 above, the terms of any insurance or the amount of cover
shall not relieve Institution or the Principal Investigator of any liabilities under this
Agreement. Where the Institution cannot cover Agents under its insurance, it shall
verify that such Agents have sufficient insurance and inform the Sponsor of such
insurance.
4.11. CRO expressly disclaims any liability in connection with the content of the
Protocol and the Investigational Product, including any liability for any product
claim arising out of a condition caused by or allegedly caused by the
administration of such product.
5. CLINICAL TRIAL SUBJECT RECRUITMENT AND ENROLLMENT
5.1.
The Principal Investigator shall make sure that the Clinical Trial Subjects (and/or
their legal representatives) will, in accordance with applicable Law, be duly
informed and that each give his informed consent prior to his participation in the
Clinical Trial. Institution will provide Sponsor/CRO an opportunity to review
and approve the content of any Clinical Trial recruitment materials (including the
ICF) directed to potential Clinical Trial Subjects before such materials are used,
regardless of medium.
5.2.
The Principal Investigator shall use reasonable endeavours to recruit the Target
within the Timelines as specified in Annex 2. As soon as the Principal
Investigator expects to reach the Target, he shall notify the Sponsor and/or CRO.
5.3.
If circumstances or events have occurred or will occur that will substantially
delay or are likely to substantially delay the progress of recruitment or enrolment
of the Clinical Trial Subjects, the Principal Investigator shall immediately inform
the Sponsor and/or CRO in writing. In each such event the Parties shall discuss
the consequences of the delay and each Party shall undertake reasonable
endeavours to agree on measures to overcome the delay.
5.4.
In the event that the Clinical Trial is part of a multi-centre clinical trial, the
Sponsor may amend the number of Clinical Trial Subjects to be recruited
pursuant to the Target as per clause 5.2 above subject to this clause 5.4.
(a) The Sponsor may require further recruitment of Clinical Trial Subjects at
the Trial Site to cease if:
 in the reasonable opinion of the Sponsor recruitment of Clinical Trial
Subjects at the Trial Site will not meet or will not likely meet the
Target within the Timelines or is proceeding at a rate below that
required to enable the relevant Timeline to be met, and upon
Sponsor’s request to increase the inclusion rate, the Principal
Investigator is unable to comply, or
 if the global recruitment target for all clinical centres of Sponsor and
its affiliates has been reached.
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(b)
Upon receipt of a notice subject to clause 5.4 (a), the Principal Investigator
shall immediately stop the recruitment and inclusion of Clinical Trial
Subjects. The terms and conditions of this Agreement regarding the
Clinical Trial Subjects shall also apply to individuals who, at the time of
receipt of such notice, have signed the ICF. Payments shall only be made
according to the number of Clinical Trial Subjects recruited and included
up to the date of receipt of the notice. The Sponsor will not take any
responsibility or have a duty to make any payment for the Clinical Trial
Subjects recruited after the date of receipt of its notice.
If recruitment of Clinical Trial Subjects is proceeding at a rate above that
required to meet the relevant Timelines the Sponsor may with the
agreement of the Principal Investigator increase the number and amend the
rate of Clinical Trial Subjects to be recruited and enrolled at the Trial Site.
6. QUALITY ASSURANCE AND CONTROL
6.1.
The Site Parties shall permit the Trial Monitor and any Auditor access to all
relevant clinical data of Clinical Trial Subjects for monitoring of the progress of
the Clinical Trial, the proper collection and recording of Clinical Trial data, the
welfare of the Clinical Trial Subjects, and altogether the good quality of the
Clinical Trial and compliance with applicable Law and Sponsor’s and/or CRO’s
Standard Operating Procedures. The Trial Monitor’s access will be arranged at
mutually convenient times and on reasonable notice.
6.2.
The Site Parties shall permit authorized representatives of the Ethics Committee
and Competent Authorities to have access to, copy and verify information
relating to the Clinical Trial, as required by and in accordance with applicable
Law. Furthermore Sponsor and/or CRO acknowledges and agrees that the
Institution executive management (or a local review board appointed by such
management) will have the right to audit the performance of the Clinical Trial at
the Trial Site. Institution acknowledges that the Clinical Trial is subject to
inspection by regulatory authorities worldwide and that such inspections may
occur after the completion of the Clinical Trial.
6.3.
In the event that the Sponsor and /or CRO reasonably believes there has been any
research misconduct in relation to the Clinical Trial, Site Parties shall provide all
reasonable assistance to any investigation into any alleged research misconduct
undertaken by or on behalf of the Sponsor and/or CRO, the results of which the
Party on whose behalf the investigation was undertaken shall, subject to any
obligations of confidentiality, communicate to the Principal Investigator. In the
event that the Principal Investigator reasonably believes there has been any
research misconduct in relation to the Clinical Trial, the Sponsor shall provide all
reasonable assistance to any investigation undertaken by or on behalf of the
Principal Investigator, the results of which shall, subject to any obligations of
confidentiality, be communicated to the Sponsor.
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6.4.
6.5.
6.6.
6.7.
6.8.
6.9.
The Site Parties shall promptly inform the Sponsor and/or CRO of any intended
or actual inspection, written enquiry and/or visit to the Trial Site by any
regulatory authority in connection with the Clinical Trial and forward to the
Sponsor copies of any correspondence from any such regulatory authority
relating to the Clinical Trial. The Site Parties shall allow Sponsor and/or CRO
representatives to be present during any such visit as permitted by Law.
The Site Parties will permit the Sponsor to examine the conduct of the Clinical
Trial and the Trial Site upon reasonable advance notice and in the company of a
Site Party’s representative, during regular business hours at mutually agreed
times, and at Sponsor's sole expense to determine that the Clinical Trial is being
conducted in accordance with the Protocol, this Agreement and applicable Law.
The Site Parties shall take appropriate measures and cause the Research Staff to
take appropriate measures and corrective actions without delay as the Sponsor
and/or CRO may reasonably require in order to solve all problems found and
reported by the Trial Monitors and any of the aforesaid Auditors, or
representatives of the Ethics Committee, Competent Authority or other
regulatory authority.
It is expressly agreed between the Parties that (a) the Sponsor will not
compensate the Principal Investigator nor any member of the Research Staff for
the assistance or guidance of representatives of the Ethics Committee, Competent
Authority or other regulatory authority and (b) the assistance or guidance of Trial
Monitors or Sponsor’s Auditors by the Principal Investigator and the Research
Staff shall be deemed included in the remuneration paid pursuant to clause 13
hereinafter unless expressly agreed otherwise in writing.
The Principal Investigator and any member of the Research Staff will be trained
by Sponsor with respect to the use of eCRFs. Before the training process, the
Principal Investigator and each member of the Research Staff shall sign an
acknowledgment agreement which shall contain statements of understanding and
acceptance of their obligations regarding the eCRF process.
The Site Parties shall ensure that all procedures defined in the Protocol are
complied with, so that all data generated at the Trial Site are reliable and have
been processed correctly (especially the randomization lists, and the blind
character of the Clinical Trial as the case may be) and will ensure that the content
of the CRFs or e-CRFs will accurately reflect source documents.
7. INVESTIGATIONAL PRODUCTS
7.1.
Parties acknowledge and agree that the Institution’s pharmacy, or such other
pharmacy as appointed by Sponsor the Principal Investigator and the Institution,
will be responsible for certain tasks in relation with the handling of the
Investigational Product. Any agreements between the pharmacy and any of the
Parties will be in writing and must be in accordance with the Institution’s internal
policies. Any such agreements will be annexed to this Agreement as applicable.
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7.2.
7.3.
Subject to the foregoing, the Sponsor and/or CRO will provide the Principal
Investigator and the pharmacy with all necessary information on the
Investigational Product(s), quality and handling instructions thereof and
sufficient quantities needed to conduct the Clinical Trial free of charge.
The Site Parties shall not use or permit the Research Staff or any third party to
use the Investigational Product for any purpose other than the conduct of the
Clinical Trial and upon termination or expiration of this Agreement all unused
Investigational Product shall, at the Sponsor’s option, either be returned to the
Sponsor or disposed of in accordance with the Protocol or the Sponsor’s written
instructions.
8. CONFIDENTIALITY
Medical Confidentiality and Samples
8.1.
It is the responsibility of each Party to effect and maintain all registrations for the
processing of Clinical Data as required by the Dutch privacy law and legislation.
Each Party shall be responsible for its own processing of personal data in
accordance with all law and regulations and with the informed consents obtained
from Clinical Trial Subjects.
8.2.
The Parties agree to adhere to the principles of medical confidentiality in relation
to Clinical Trial Subjects.
8.3.
Sponsor acknowledges that Clinical Trial Subjects – and/or their legal
representatives on their behalf – may withdraw or change their initial informed
consent. Principal Investigator shall promptly notify Sponsor of any withdrawal
of or changes in the informed consent of a Clinical Trial Subject, which may
affect the use of such Clinical Trial Subject’s Clinical Data under this
Agreement. The Principal Investigator will communicate with Sponsor on behalf
of the Clinical Trial Subject. However, the procedure followed upon a
withdrawal of a Clinical Trial Subject’s consent will be according to the
instructions in the Protocol and the ICF.
8.4.
Sponsor shall refrain from tracing and/or identifying any Clinical Trial Subject.
In the event any Clinical Trial Subject, for whatever reason, becomes identifiable
to Sponsor, Sponsor agrees to preserve, at all times, the confidentiality of
information pertaining to such Clinical Trial Subjects. Sponsor shall adopt
appropriate technical and organizational measures to prevent any unauthorized or
accidental use, access or processing of clinical data and/or Samples (Security
Breach). Security Breaches shall be reported to the Principal Investigator
promptly.
Confidential Information
8.5.
The Receiving Party shall ensure that only those of its officers and employees
(and those of its Affiliates and members of the Research Staff) and Agents
directly concerned with the carrying out of this Agreement have access to the
Confidential Information of the Disclosing Party. The Receiving Party shall take
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8.6.
all practicable steps to ensure that such persons abide by the same obligations of
confidentiality as apply to the Receiving Party under this Agreement. The
Receiving Party undertakes to treat as strictly confidential and not to disclose to
any third party any Confidential Information of the Disclosing Party, except
where disclosure is required by a regulatory authority or by law, in which case
the Receiving Party shall inform the Disclosing Party of such requirement and
the information to be disclosed and Disclosing Party take reasonable steps to
limit the scope of such disclosure. Notification will be within a reasonable time
prior to being required to make the disclosure or if such time is not available,
immediately upon becoming known of the requirement to disclose Confidential
Information. The Receiving Party undertakes not to make use of any Confidential
Information of the Disclosing Party, other than in accordance with this
Agreement, without the prior written consent of the Disclosing Party.
The obligations of confidentiality and non-use set out in clause 8.5 shall not
apply to information which:
a. is or becomes part of the public domain by any other means than a wrongful
act or breach of this Agreement by the Receiving Party;
b. was or becomes in the Receiving Parties’ lawful possession prior to the
disclosure without restriction on disclosure as evidenced by written records;
c. has been independently developed by the Receiving Party without the use of
Confidential Information of the Disclosing Party as evidenced by written
records;
d. has been obtained by the Receiving Party from a third party who is not
subject to a duty of confidentiality; or
e. is published in accordance with clause 11 hereof.
Principal Investigator and Research Staff’s Personal Information
8.7.
Principal Investigator and Research Staff understand and agree that their personal
information including name, contact details, financial information relating to,
among other matters, compensation and reimbursement payments for study
conduct, and other personal data of the Principal Investigator and Research Staff
in connection with Principal Investigator's and Research Staff’s conduct of the
Clinical Trial will be processed both by computer and manually, by Sponsor and
its Affiliates and Agents in order to comply with Sponsor's and its Affiliates'
obligations imposed by law, guidance or regulatory authorities and for
considering from time to time potential investigators for future studies or
organizing safety reporting. Principal Investigator and Research Staff further
understand and agree that their personal data may, if necessary for these
purposes, be made available to regulatory authorities and ethics committees.
Principal Investigator and Research Staff understand and agree that the Sponsor’s
use and disclosure of their personal data may involve use and disclosure in
countries other than that where the Principal Investigator and Research Staff are
located. Such countries may include but not be limited to: the United States,
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Japan, Canada, Australia, New Zealand, Switzerland, or countries in Latin
America or Asia. Principal Investigator and Research Staff further understand
that not all countries to which personal information may be transferred offer an
equivalent level of protection of privacy of personal information. Principal
Investigator is entitled to review their personal data held by Sponsor or its
Affiliates upon request and to have such data corrected if necessary.
9. INTELLECTUAL PROPERTY
9.1.
All Intellectual Property Rights and Know How owned by or licensed to any of
the Parties prior to and after the date of this Agreement other than any
Intellectual Property Rights and Know How arising from the Clinical Trial are
and shall not be affected by this Agreement.
9.2.
The Sponsor shall own the Intellectual Property Rights and Know How arising
from and directly related to the Clinical Trial, the Protocol (Sponsor Intellectual
Property and Know How) and the Investigational Product (including but not
limited to its formulation and use alone or in combination with other drugs), but
excluding (1) any clinical procedure and improvements thereto that are clinical
procedures of the Institution and/or Principal Investigator and (2) copyrights on
work published by the Principal Investigator in accordance with clause 11
hereinafter, which copyrights shall either vest in the Institution or, if made by the
Principal Investigator and other authors, in the Institution and the other coauthor(s) in accordance with applicable copyright laws or as mutually agreed
between the Parties, or shall vest in the publisher of such work upon the transfer
of copyrights by the author(s).
9.3.
The Site Parties will promptly inform the Sponsor of any invention or discovery
arising from and directly related to the Clinical Trial, the Investigational Product
(including but not limited to its formulation and use alone or in combination with
other drugs) or the Protocol, and Institution and/or Principal Investigator hereby
assigns and transfers, and shall procure that the Research Staff shall assign and
transfer, without additional consideration, all assignable rights and title in
relation to such Intellectual Property Rights and Know How, and will provide
reasonable assistance to the Sponsor in filing or prosecuting Intellectual Property
Rights, at the expense of the Sponsor.
9.4.
Nothing in this clause 9 shall be construed so as to prevent or hinder the
Institution or the Principal Investigator from using the Sponsor Know How
generated in the Clinical Trial for its internal hospital and non-commercial
research activities to the extent such use does not result in the disclosure or
misuse of Confidential Information or the infringement of any Intellectual
Property Rights of the Sponsor.
9.5.
In case a third party brings a claim or initiate proceedings against the Site Parties
for the use of Intellectual Property of Sponsor in conducting the Clinical Trial in
accordance with this Agreement, Sponsor shall indemnify the Site Parties against
such claims or proceedings, provided the Site Parties shall have notified Sponsor
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promptly in writing of it and shall, upon Sponsor’s request and at Sponsor’s
costs, have permitted Sponsor to have full care and control over the claim or
proceeding using legal representation of its own choosing in accordance with
clause 4.3-4.5.
10. PUBLICITY
10.1. The Sponsor and/or CRO will not use the logo or name of the Site Parties, nor of
any member of the Research Staff, in any publicity, advertising or news release
without the prior written approval of the Site Parties, such approval not to be
unreasonably withheld.
10.2. The Site Parties will not, and will ensure that the Research Staff will not, use the
name or logo of the Sponsor and/or CRO or of any of its employees, nor the
name of the Clinical Trial, nor the name of the Investigational Product, in any
publicity, advertising or news release without the prior written approval of the
Sponsor and/or CRO, such approval not to be unreasonably withheld.
10.3. The Site Parties will not issue and will ensure the Research Staff will not issue
any information or statement to the press or public, including but not limited to
advertisements for the enrolment of Clinical Trial Subjects, without, where
appropriate, the review and the delivery of a favourable opinion from the Ethics
Committee and the prior written permission of the Sponsor and/or CRO.
10.4. Unless required by Law, Parties shall not disclose terms of this Agreement
without the prior written approval of the other Party.
11.
PUBLICATION AND AUTHORSHIP
Principles
11.1 The Sponsor, Institution and the Principal Investigator each acknowledge the
importance of public disclosure/publication of information collected or generated
as a result of or related to the Clinical Trial, under the condition that public
disclosure/publication takes place under the provisions of this clause 11.
11.2 Upon completion of the Clinical Trial (whether prematurely or otherwise) the
Principal Investigator and Sponsor shall co-operate in producing a report of the
Clinical Trial detailing the methodology, results and containing an analysis of the
results and drawing appropriate conclusions.
Publication by Sponsor
11.3 The Site Parties each acknowledge that the Sponsor may present at symposia,
national or regional professional meetings, and publish in journals, theses or
dissertations, or otherwise of their own choosing, methods and results of the
Clinical Trial and in particular, but without limiting the foregoing, post a
summary of Clinical Trial results in on-line clinical trials register(s) before or
after publication by any other method. In the event the Sponsor coordinates a
multi-centre publication, the participation of the Principal Investigator or other
representatives of the Institution as a named author shall be determined in
accordance with generally accepted academic standards for authorship as outlined
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in 11.8 below. If the Principal Investigator or other representative of the
Institution is a named author of the multi-centre publication, such person shall
have access to the Clinical Trial data from all Clinical Trial sites as necessary to
participate fully in the development of the multi-centre publication.
Publication by Principal Investigator
11.4 The Sponsor agrees that the Principal Investigator shall be permitted to present at
symposia, national or regional professional meetings, and to publish in journals,
theses or dissertations, or otherwise of its own choosing, methods and results of
the Clinical Trial, subject to this clause 11 and any publication policy described in
the Protocol, provided any such policy does not obstruct publication
unreasonably. Principal Investigator shall appropriately disclose Sponsor’s role in
the Clinical Trial in any such publication or presentation.
11.5 If the Clinical Trial is a multi-centre Clinical Trial, any publication based on the
results obtained at the Trial Site (or a group of sites) shall not be made before the
first multi-centre publication or presentation unless otherwise agreed in writing. If
a publication concerns the analyses of sub-sets of data from a multi-centre
Clinical Trial the publication shall make reference to the relevant multi-centre
publication(s). Notwithstanding the foregoing, if a multi-centre publication is not
published within twelve (12) months after completion of the Clinical Trial and
lock of the Clinical Trial database at all research sites that are part of the multicentre Clinical Trial or any earlier termination or abandonment of the Clinical
Trial, the Principal Investigator shall have the right to publish or present the
methods and results of the Clinical Trial in accordance with the provisions of this
clause 11. The foregoing provided however, that any such publication will take in
account the rights and interests of all investigators involved in the multi-centre
Clinical Trial and authorship will be determined in accordance with clause 11.8.
11.6 Material for public dissemination will be submitted to the Sponsor for review at
least thirty (30) days prior to submission for publication, public dissemination, or
review by a publication committee. If Sponsor does not respond within this period
Institution and/or the Principal Investigator is/are free to proceed with the
intended publication or presentation without further delay.
11.7 During the thirty (30) period for review of a proposed publication referred to in
clause 11.6 above, the Sponsor shall be entitled to
a.
comment on the scientific content of the proposed publication. The
Principal Investigator agrees that all reasonable comments made by the
Sponsor in relation to a proposed publication or presentation will be
incorporated into the publication or presentation. Reasonable comments for
the purposes of this clause 11.7 shall mean such comments and suggestions
that, with a view to the scientific interest or the treatment of patients, will
clarify or improve the proposed publication or presentation of the results of
the Clinical Trial or the conclusions drawn from such results, and such other
comments that aim to avoid that such publication or presentation will
misrepresent the results;
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b.
make a reasoned request to the Principal Investigator that publication be
delayed for an additional period of sixty (60) days (following the 30 day
period referred to in clause 11.6) in order to enable the Sponsor to take steps
to protect its proprietary information and/or Intellectual Property Rights and
Know How, and the Principal Investigator shall not unreasonably withhold
its consent to such a request; and
c.
may cause the Principal Investigator to remove from the projected
publication any Sponsor Confidential Information received by Principal
Investigator that are not constituted results of the Clinical Trial. The
Institution shall not unreasonably withhold or delay its consent to the
reasoned request from the Sponsor.
Authorship and Copyrights
11.8 Publications will be in accordance with international recognized scientific and
ethical standards concerning publications and authorship, including the Uniform
Requirements for Manuscripts Submitted to Biomedical Journals, established by
the International Committee of Medical Journal Editors. Copyrights concerning
Publications of the Clinical Trial remain with the authors of the Publication,
regardless of any other provisions regarding intellectual property rights.
12.
TERM AND TERMINATION
12.1
This Agreement commences on the Effective Date and shall continue in force
until the earlier of:
a. completion of final Clinical Study Report and the final payment under this
Agreement; or
b. early termination in accordance with clauses 12.2, 12.3 or 12.5 of this
Agreement;
12.2
Each Party may terminate this Agreement upon written notice to the other
Parties with immediate effect in the following events:
a. if the approval by the Ethics Committee in charge of the Clinical Trial is not
granted or irrevocably revoked;
b. if it can be reasonably concluded that the Clinical Trial must be terminated
in the interests of the health of the Clinical Trial Subjects;
c. If it becomes apparent, following confirmation of the Ethics Committee or
the Independent Committee, that continuation of the Clinical Trial cannot
serve a scientific purpose, and this is notified to the Ethics Committee;
d. if the Sponsor and/or the Institution and/or the Principal Investigator
become or are declared insolvent or a petition in bankruptcy has been filed
against it or if one of them is dissolved;
e. if circumstances beyond a Party’s control occur that render continuation of
the Clinical Trial unreasonable as outlined in Clause 16;
f. if one of the parties fails to comply with the obligations arising from the
Agreement and, if capable of remedy, is not remedied within 30 days after
receipt of notice from the other Party specifying the non-compliance and
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12.3
12.4
12.5
12.6
12.7
12.8
12.9
13.
requiring its remedy, unless failure to comply is not in reasonable
proportion to the premature termination of the Clinical Trial.
Sponsor and/or CRO may terminate this Agreement if the Principal Investigator
is no longer able (for whatever reason) to act as Principal Investigator and no
mutually acceptable replacement has been found in accordance with Clause 2.3,
provided that the Sponsor will not unreasonably withhold its approval of the
proposed replacement of Principal Investigator.
In all circumstances causing the early termination of this Agreement pursuant to
clauses 12.2 or 12.3 above, the Sponsor shall confer with the Principal
Investigator and use their best endeavours to minimise any inconvenience or
harm to Clinical Trial Subjects caused by the premature termination of the
Clinical Trial. Parties agree that in case of early termination of this Agreement,
they will in good faith try to make arrangements concerning the continuation of
the treatment of the enrolled patients if such is in their medical best interest.
Up until a Clinical Trial Subject has signed the ICF, Sponsor and/or CRO may
terminate this Agreement upon written notification to the Principal Investigator
and the Institution, with immediate effect, in the following events:
a.
for lack of recruitment at the Trial Site in case the Clinical Trial is
conducted at one Site only; or
b.
in case of a multicentre trial, if termination at the Trial Site does not
affect performance of the Protocol.
Upon notice of termination of this Agreement, Site Parties will not recruit and/or
enroll additional Clinical Trial subjects, and will cooperate with the Sponsor in
the orderly discontinuation of the Clinical Trial, including, without limitation,
discontinuing Investigational Product as soon as medically appropriate, allowing
Sponsor and/or CRO access to records and facilities for Clinical Trial close-out
procedures, and requiring Principal Investigator to complete any actions
required by the role Principal Investigator.
In case of early termination of this Agreement, the financial provisions of 13.3
shall apply.
At close-out of the Trial Site following termination or expiration of this
Agreement the Site Parties shall immediately deliver to the Sponsor all
Confidential Information, except for copies to be retained in order to comply
with Institution’s archiving obligations or for evidential purposes. Furthermore
the Site Parties shall immediately deliver to the Sponsor any equipment
provided to them pursuant to the terms and conditions of Annex 5.
Termination of this Agreement will be without prejudice to the accrued rights
and liabilities of the Parties under this Agreement.
FINANCIAL PROVISIONS
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13.1
13.2
13.3
13.4
The Sponsor (through CRO, if applicable) will provide funding in support of the
Clinical Trial, as set out in Annex 3. All payments shall occur on the conditions as
set out in this Annex 3.
In the event that amendments to the Protocol require changes to the Clinical Trial
financing arrangements, an amended financial schedule will be agreed upon and
signed by the Parties which will replace the existing Annex 3.
If the Agreement is terminated for one of the reasons in clauses 12.2, 12.3 or 12.5,
except for material breach by the Institution and/or the Principal Investigator
under clause 12.2 (f), and subject to an obligation on the Institution and the
Principal Investigator to mitigate any loss, the Sponsor (through CRO, if
applicable) shall pay all fees and expenditures falling due for payment to the
Principal Investigator and/or the Institution up to the date of termination in
accordance with Annex 3, and also all expenditure falling due for payment after
the date of termination which arises from uncancellable commitments reasonably
and necessarily incurred by the Principal Investigator and/or Institution for the
performance of the Clinical Trial prior to the date of termination, in accordance
with Annex 3. In the case of termination for material breach by the Institution
and/or the Principal Investigator under clause 12.2 (f), and subject to an
obligation on the Institution and the Principal Investigator to mitigate any loss,
Sponsor (through CRO, if applicable) shall pay all fees and expenditures falling
due for payment of properly performed services up to the date of the material
breach by the Institution and/or the Principal Investigator in accordance with
Annex 3. In case of termination for fraud, bribery or corruption, Sponsor will not
pay for fees and expenditures directly related to such fraud, bribery or corruption.
In the event of early termination, if payment has been made by the Sponsor
(through CRO if applicable) to the Institution or the Principal Investigator in
advance for work not completed in accordance with Article 13.3, the Institution
and/or the Principal Investigator shall issue a credit note and repay the remainder
of the monies within 45 days of receipt of written notice from the Sponsor and/or
CRO
14. MISCONDUCT AND DEBARMENT
14.1 The Institution and/or Principal Investigator represent and warrant that neither the
Principal Investigator nor, to their best knowledge, any collaborator of the
Principal Investigator involved in conducting the Clinical Trial nor any member of
the Research Staff, has been debarred, excluded, disqualified or restricted in their
ability to practice medicine, participate in a clinical trial, or perform services in
connection with the evaluation of a pharmaceutical product under any laws,
regulations or professional code of conduct including without limitation United
States Code of Federal Regulations (“U.S.C.” or “CFR”) title 21 section §335a
and section §312.70.
14.2 The Institution and/or Principal Investigator shall immediately notify Sponsor
should the Principal Investigator or any collaborators or any member of the
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Research Staff involved in conducting the Clinical Trial, be so debarred, excluded,
disqualified or restricted, or should a procedure or action be initiated against any
of them that could result in their being so debarred, excluded, disqualified or
restricted, at any time during the term of this Agreement and during the twelve
months following the expiration or termination of the Agreement.
15. DISCLOSURE OF FINANCIAL INTEREST
15.1 Principal Investigator shall ensure that he/she and collaborators and any member
of the Research Staff involved in this Clinical Trial at Principal Investigator’s
Clinical Trial Site provide Sponsor with the appropriate financial disclosures
required for Sponsor’s compliance with CFR title 21 Part 54, on Sponsor’s request
and on such forms as Sponsor may supply or approve.
15.2 During the term of this Agreement and for one (1) year following termination or
completion of the Clinical Trial, Principal Investigator shall promptly notify
Sponsor of any material change in the information disclosed on a previous form .
15.3 Parties may disclose the financial terms of this Agreement only if required by Law
or transparency regulations.
16. FORCE MAJEURE
No Party shall be liable to the other Parties or shall be in default of its obligations
hereunder if such default is the result of war, hostilities, terrorist activity,
revolution, civil commotion, strike, fire, flood, and epidemic or because of any
other cause beyond the reasonable control of the Party affected. The Party affected
by such circumstances shall promptly notify the other Parties in writing when such
circumstances cause a delay or failure in performance and where they cease to do
so. However, such non-performance or delay is excused under this provision only
for the duration of the qualifying event.
17. GOVERNING LAW AND DISPUTE RESOLUTION
This Agreement shall be governed by, and construed in all respects in accordance
with the laws of The Netherlands without regard to its conflicts of laws rules. Any
claims, controversies or disputes arising out of or in connection with this
Agreement which cannot be settled amicably between the Parties, shall be subject
to the exclusive jurisdiction of the competent court in The Netherlands.
18. HUMAN SAMPLES
18.1 As part of the Protocol, Samples may be transferred to Sponsor or another
organization indicated by Sponsor only if this is arranged for in the ICF.
18.2 Sponsor, and the other organization mentioned above in this clause 18.1, shall
have the right to store, transfer and use the Samples only in accordance with the
applicable Law, the Protocol and ICF (as approved by the ethics committee).
Principal Investigator shall promptly notify Sponsor of any withdrawal of or
changes in the informed consent of a Clinical Trial Subject, which may affect the
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18.3
18.4
19.
use of such Clinical Trial Subject’s Samples under this Agreement. In such event,
Sponsor shall destroy or return the affected Samples if necessary.
Upon termination or expiration of the Clinical Trial, and at least at any time the
Samples are no longer needed to be retained by Sponsor for any pending
registration purpose related to the Study Drug in relation to the Protocol or as
defined in the ICF, or as required per any Applicable Law or regulation, the
remainder of the Samples in Sponsor’s or any of its designee’s possession will be
returned to the Site Parties, retained by the Sponsor in accordance with clause
18.3 or destroyed by the Sponsor, as described in the Protocol and/or the ICF.
For the avoidance of any doubt, the control (in Dutch: zeggenschap) of the
Samples remains at all times at the Clinical Trial Subjects they are derived from,
with the Institution and/or Sponsor acting as custodian of the Samples, as
described in the Protocol.
MISCELLANEOUS
19.1 Sponsor and CRO shall have the right to assign this Agreement to an Affiliate
upon prior written notification to Institution. Institution shall have the right to
assign this Agreement to an Affiliate upon prior written approval from Sponsor or
CRO, which approval shall not be withheld unreasonably. In all other
circumstances, neither Party shall assign its rights or duties under this Agreement
to another party without prior written consent of the other Party, except that the
Sponsor may assign this Agreement to any of its Affiliates or to the successor
(including the survivor company of any consolidation or merger) or assignee of
all or substantially all of its business. Any approval by a Party of an assignment,
transfer or encumbrance by the other Party shall not release the assigning Party of
any of its obligations under this Agreement due up until such assignment. Subject
to the foregoing, this Agreement shall bind and inure to the benefit of the
respective Parties and their successors and assignees.
19.2 Institution or the Principal Investigator may not sub-contract the performance of
all or any of its obligations under this Agreement without the prior written
consent of the Sponsor and/or CRO, such consent not to be unreasonably withheld
or delayed. Any Party who so sub-contracts shall be responsible for the acts and
omissions of its sub-contractors as though they were its own.
19.3 Nothing shall be construed as creating a joint venture, partnership or contract of
employment between the Parties.
19.4 Any agreement to amend, vary or modify the terms of the Agreement in any
manner shall be valid only if effected in writing and signed by duly authorized
representatives of each of the Parties hereto. A facsimile transmission of this
signed Agreement or email transmission of a PDF of this signed Agreement
bearing a signature on behalf of a Party will be legal and binding on such a Party.
19.5 Should there be any inconsistency between the Protocol and the terms of this
Agreement, or any other document incorporated therein, the Protocol shall prevail
in case such inconsistency concerns clinical matters and the Agreement shall
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19.6
19.7
19.8
prevail the inconsistency concerns non-clinical matters. For the avoidance of
doubt, Termination and Publication provisions of this Agreement shall always
prevail above the Protocol.
Unless otherwise agreed, formal notices to the respective Parties required by this
Agreement shall be given, made or served if in writing and delivered personally
or sent by registered mail or by facsimile with receipts confirmed to the contact
details as set out in Annex 7. Other communication between the Parties may also
be effected by other means such as e-mail with acknowledgement of receipt,
which fulfils the conditions of written form. Change of the contact details has to
be notified to the other Party or Parties, but shall not require amendment of this
Agreement.
The clauses 4 (Liabilities, Indemnification and Insurance); 6.1 and 6.4 (Quality
Assurance and Control); 7.3 (Use of Investigational Product); 8.1-8.4 (Medical
Confidentiality).; 9 (Intellectual Property); 10 (Publicity); 11 (Publication); 12.4
and 12.5-12.10 (Termination); 13.3 and 13.4 (Financial Provisions); 14
(Misconduct and Debarment); 15 (Disclosure of Financial Interest); 16 (Force
Majeure); 17 (Governing Law and Dispute Resolution); 18 (Human Samples) and
this clause 19.7 (Surviving Clauses) or other clauses contemplating performance
after termination, shall survive termination or expiry of this Agreement. The
provisions of clause 8.5 (Confidential Information) shall remain in force for a
period of ten (10) years.
Each person signing this Agreement represents and warrants that he or she is duly
authorized and has legal capacity to execute and deliver this Agreement. Each
party represents and warrants to the other that the execution and delivery of the
Agreement and the performance of such party's obligations hereunder have been
duly authorized and that the Agreement is a valid and legal agreement binding on
such party and enforceable in accordance with its terms.
Annexes
Annex 1: Protocol
Annex 2: Timelines
Annex 3: Financial arrangements
Annex 4: Pharmacy agreement
Annex 5: Equipment
Annex 6: Bribery and Corruption Statement
Annex 7: Contact details
Annex 8: Power of Attorney / Delegation of Authority to CRO
[The remainder of this page is intentionally left blank; for signatures, see next page]
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Signed on behalf of the Sponsor / CRO
Signature:
…………………………………………
Name: ……………………………
Title: ……………………………
Date: …………………………………………
Signed on behalf of the Institution
Signature:
…………………………………………
Name: ……………………………
Title: ……………………………
Date: …………………………………………
The undersigned Principal Investigator hereby declares that he/she has read the above
Agreement between the Parties and that he/she agrees with the provisions of the Agreement
relative to his/her role, responsibilities and duties concerning the Clinical Trial:
Signed by the Principal Investigator
Signature:
…………………………………………
Name: ……………………………
Title: ……………………………
Date: …………………………………………
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ANNEX 1
PROTOCOL
(by reference only)
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ANNEX 2
TIMELINES
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ANNEX 3
FINANCIAL ARRANGEMENTS
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ANNEX 4
PHARMACY AGREEMENT
Template Clinical Trial Agreement version July 2015
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ANNEX 5
EQUIPMENT
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ANNEX 6
BRIBERY AND CORRUPTION
(A)
The Trial Parties must at all times act with integrity and honesty and comply with the highest
ethical standards.
(B)
The Trial Parties must not make, give, or offer any payment, gift or other benefit or advantage to
any person for the purposes of:
(i)
securing any improper advantage; or
(ii)
inducing the recipient or another person to do or omit to do any act in violation of their duties or
responsibilities (or for the purposes of rewarding such conduct).
This restriction applies at all times and in all contexts. For the avoidance of any doubt, it applies both to
dealings with "public officials" and to dealings with employees and agents of commercial enterprises.
(C)
Nevertheless, particular care must be exercised with dealings with public officials. The Trial
Parties must not make, give or offer any payment, gift or other benefit or advantage for the purposes of
influencing any act or decision of a public official (or inducing such official to use their influence with
another person, entity or government instrumentality or to affect or influence any act or decision of such
other person, entity or government instrumentality).
(D)
The term "Public Official" includes any person acting on behalf of any government department,
agency or instrumentality or any state-owned or controlled enterprise. By way of example, this includes
health care professionals employed by a state- or local municipality-run hospital or clinic, and
representatives of public international organizations.
(E)
The Trial Parties must not make, give or offer any payment, gift or other benefit or advantage to
any person whilst knowing or suspecting that all or a portion of such money, gift, benefit or advantage
will be used, whether directly or indirectly, in breach of (B) or (C) above.
(F)
The Trial Parties shall make and keep books, records, and accounts, which, in reasonable detail,
accurately and fairly reflect the transactions and dispositions of the assets of the Trial Parties.
(G)
The Trial Parties shall
devise and maintain a system of internal accounting controls sufficient
to provide reasonable assurances that –
(i)
(ii)
transactions are executed in accordance with management’s general or specific authorization;
transactions are recorded as necessary
(I)
to permit preparation of financial statements in conformity with generally accepted
accounting principles or any other criteria applicable to such statements, and
(II)
to maintain accountability for assets;
(iii)
access to assets is permitted only in accordance with management’s general or specific
authorization; and
(iv)
the recorded accountability for assets is compared with the existing assets at reasonable intervals
and appropriate action is taken with respect to any differences.
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ANNEX 7
CONTACT DETAILS
Recipients of Notice in accordance with clause 19.6 of this Agreement:
1) If to Sponsor / CRO
For scientific matters:
Name:
Address:
Tel.:
Mail:
For legal matters:
Name:
Address:
Tel.:
Mail:
For financial matters:
Name:
Address:
Tel.:
Mail:
2) If to Institution / Principal Investigator
For scientific matters:
Name:
Address:
Tel.:
Mail:
For legal matters:
Name:
Address:
Tel.:
Mail:
For financial matters:
Name:
Address:
Tel.:
Mail:
Template Clinical Trial Agreement version July 2015
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ANNEX 8
POWER OF ATTORNEY / DELEGATION OF AUTHORITY TO CRO
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